So I'm Derick Raal, I'm an endocrinologist based in Johannesburg, South Africa. But I've always been interested in lipid and lipid disorders, particularly in a condition called familial hypercholesterolemia because in South Africa we have quite a high prevalence of the condition. So people don't sort of understand that familial hypercholesterolemia is actually one of the commonest inherited disorders. It affects about 1 in every 300 people worldwide, so there's about 30 million people affected with familial hypercholesterolemia.

What was the reasoning and the design behind the study?

So the standard treatment for familial hypercholesterolemia, these are patients with very high LDL cholesterol levels. We use high intensity statins, we add ezetimibe, but despite that therapy, we can't get these patients to the currently recommended LDL cholesterol targets. So we need further therapies.

So there are two PCSK9 inhibitors available. They're monoclonal antibodies which need to be administered once every two weeks. They need to be refrigerated. So I presented results of a study with a new, it's not a monoclonal antibody, it's actually a small fusion protein, so it's called a monobody. It doesn't have to be refrigerated, and it can be given once a month as opposed to every two weeks. So it's a very novel, what we call a third generation PCSK9 inhibitor.

So in the LIBerate open-label extension study, we looked at patients that clinically or genetically had familial hypercholesterolemia. There were about 703 patients in the trial program, and we looked at how they responded to this drug called lerodalcibep, this novel PCSK9 inhibitor, during 72 weeks of open label extension. And we found that the therapy reduced the LDL cholesterol a further 50%, which allowed the vast majority of these patients to achieve the new LDL target. So 80% had a 50% or greater reduction in LDL cholesterol, and about 70% of these difficult to treat patients achieve the currently recommended LDL cholesterol targets.

What are the take-home messages for practice?

Well, first of all, I think FH is an asymptomatic condition and it's often forgotten about. So in any patient who presents with a premature myocardial infarction, a stroke, you need to take a family history and think about this condition because it's most important to treat early and to treat aggressively in terms of reducing their risk.

The average age of onset of heart attack in a male with FH is actually 41 – it's about 10 years later in females. So the real take-home message is that the current therapies don't get the LDL low enough. And we have to add PCSK9 inhibitors, which are a remarkable class of drugs. The advantage of this additional therapy is hopefully it's easier to use because it's a monthly injection and because it doesn't have to be refrigerated. So it adds to our armamentarium for treating these quite difficult to treat patients.

What further research is needed in this area?

So we've now got to the end of the phase three studies looking at patients with familial hypercholesterolemia with established atherosclerotic cardiovascular disease or high risk. But ultimately, we've got to do a cardiovascular outcome trial to really show that we reduced cardiovascular events. So that's planned for next year. Hopefully the cardiovascular outcome study will start in the new year.